It is known that a worsened hyperglycemic state causes various diseases, and the state is referred to as diabetes. In Japan, it is said that there are more than sixteen millions of patients in the prediabetic state (so-called borderline patients), and in view of the current lifestyle habits, the number of the patients is expected to continue to increase in the future. In order to prevent development of diabetes caused by the hyperglycemic state, blood glucose levels must be controlled in the long term.
The hyperglycemic state is a state where blood glucose levels are beyond the normal range, and the normal range is a state of a fasting blood glucose level: 110 mg/dl or less, a blood glucose level one hour after loading of 75 g of sugar: 160 mg/dl, and a blood glucose level two hour after loading of 75 g of sugar: 120 mg/dl or less (Non-Patent Document 1).
Hemoglobin A1c, a binding substance of glucose and hemoglobin, increases depending on the degree of hyperglycemia. Because hemoglobin A1c once produced does not disappear until the life span of erythrocyte (120 days) ends, it reflects the past blood glucose control conditions over a long period of time (Non-patent document 1).
Further, α-glucosidase inhibitors, sulfonylurea drugs as insulin secretagogues, thiazolidine derivatives as insulin resistance improving agents and the like are currently used as therapeutic agents for diabetes. However, the drug efficacies thereof are not satisfactory, and they suffer many problems such as side effects causing coma due to rapid drop in blood glucose level. Meanwhile, as a drug including a naturally-derived ingredient having an effect of suppressing an increase in a blood glucose level, the prior art references have disclosed a hyperglycemia suppressing agent containing a banaba-derived ingredient (Patent document 1), a hyperglycemia suppressing agent containing a concentrated extract of fermentation product of wheats or barleys as an active ingredient (Patent document 2) and the like.
Phytosterols are broadly classified into three groups: 4-desmethylsterols; 4-monomethylsterols; and 4,4-dimethylsterols. Examples of 4-desmethylsterols include generally widely known cholesterol, campesterol, brassicasterol, sitosterol, stigmasterol, and fucosterol, examples of 4-monomethylsterols include lophenol and foliol, and examples of 4,4-dimethylsterols include cycloartanol and lupeol.
As methods of producing those phytosterols, there have been disclosed a method of collecting phytosterols with methanol from rape oil and soybean oil, and a method that includes immersing crude phytosterols in an organic solvent and separating the organic solvent to separate β-sitosterol, stigmasterol, campesterol, and brassicasterol (Patent Document 3).
There have been disclosed methods of producing 4,4-dimethylsterols, which include: a method of producing cycloartenol and 24-methylenecycloartanol (which is a conventional name of 24-methylene-9,19-cyclolanostan-3-ol) (Patent Document 4); and a method of producing cycloartenol ferulate from γ-oryzanol and a method of synthesizing a compound using a hydrolysate thereof as a starting substance (Patent Document 5). However, a method of producing 4-monomethylsterols, in particular, a compound having a lophenol skeleton has been unknown.
As a techniques for isolating phytosterols by a supercritical fluid extraction method, a one- and two-stage supercritical fluid extraction technique for concentrates of carotene, vitamin E, and other minor ingredients has been disclosed. For example, there have been disclosed a method of extracting phytosterols (campesterol, stigmasterol, β-sitosterol) in natural fat and oil (Patent Document 6), a method of producing phytosterols in the Amorphophallus konjac by a supercritical fluid extraction method, and a hypocholesterolemic agent, a prostatic hypertrophy improving agent, and a food or drink including the same (patent Document 7), and the like.
The genus Aloe in the family Liliaceae is a group of plants including Aloe vera (Aloe barbadensis Miller) and Aloe arborescens (Aloe arborescens Miller var. natalensis Berger), and the like, and they are empirically known to have various efficacies. The prior arts regarding a blood glucose level improving effect of those efficacies of plants of the genus Aloe include: clinical studies in the United States (Non-Patent Document 2); a hypoglycemic action observed in animal studies (Non-Patent Documents 3 or 4); and a hypoglycemic action of polysaccharides in plants of the genus Aloe (Patent document 8). Moreover, an Aloe vera squeezed liquid and a hypoglycemic agent containing the squeezed liquid as an active ingredient (Patent Document 9) have been disclosed.
Meanwhile, as techniques for extracting an active ingredient in Aloe having a blood glucose level improving effect, the following techniques have been disclosed. For example, the techniques include: a method of producing an Aloe vera gel stock solution, which includes sterilization with chlorine, superheating at 90° C., and filtration (Patent Document 10); a method of producing an Aloe vera gel squeezed liquid which is characterized in that all steps are carried out at 75° C. or lower (Patent Document 11); an Aloe vera squeezed liquid obtained by squeezing and filtration steps and by a treatment using activated carbon, diatom earth, and a sterilization filter, while controlling heating to 60° C. for 30 minutes in all production steps (Patent Document 12); and a method of producing Aloe products which includes: preparing an Aloe juice from leaves of an Aloe plant; adjusting the pH of the juice to 3 to 3.5; precipitating activated substances by adding a water-soluble lower aliphatic polar solvent to form a heterogeneous solution; and removing the water-soluble lower aliphatic polar solvent and solubilized substances to isolate the precipitated activated substances (Patent Document 13).
Also disclosed are a technique for producing an extract having an immunodepression-improving effect by: ultracentrifuging Aloe vera; collecting an ethanol-dissolved part of the resultant supernatant; and performing distribution extraction of the fraction with butanol (Patent Document 14) and a technique for producing a prophylactic and improving agent for obesity by performing distribution extraction of an aqueous solution of an Aloe squeezed liquid or solvent extract with ethyl acetate or butanol (Patent Document 15).
Patent Document 1: JP 2003-95941 A
Patent Document 2: JP 2002-371003 A
Patent Document 3: JP 2002-542161 A
Patent Document 4: JP 57-018617 A
Patent Document 5: JP 2003-277269 A
Patent Document 6: JP 2005-87998 A
Patent Document 7: JP 2003-113394 A
Patent Document 8: JP 60-214741 A
Patent Document 9: JP 2003-286185 A
Patent Document 10: JP 2002-68997 A
Patent Document 11: JP 2002-284661 A
Patent Document 12: JP 2002-205955 A
Patent Document 13: JP 2832551 B
Patent Document 14: JP 08-208495 A
Patent Document 15: JP 2000-319190 A
Non-Patent Document 1: Nippon Rinsho, No. 808, Vol. 2, pp. 405-409, 2002
Non-Patent Document 2: Phytomedicine, Vol. 3, pp. 245-248, 1996
Non-Patent Document 3: Phytotherapy Research, Vol. 15, pp. 157-161, 2001
Non-Patent Document 4: Phytotherapy Research, Vol. 7, pp. 37-42, 1993